PROJECT SUMMARY: Exposure to a complex mix of environmental stressors during critical fetal and childhood development periods is an important yet understudied area of public health, particularly when coupled with psychosocial and other factors that may modify the effects of these exposures. Existing studies usually investigate the effect of single toxicants or exposures and so do not reflect the reality that children experience combinations of exposures simultaneously. To address this gap, the proposed Environmental Influences on Child Health Outcomes in Puerto Rico (ECHO-PRO) will leverage and build upon an active birth cohort in Puerto Rico (?PROTECT?, P42ES017198) that has recently initiated infant/child follow-up (?CRECE?, P50ES026049). ECHO-PRO will provide data and biospecimens for 570 mother-child pairs already participating in the PROTECT/CRECE cohort, as well as recruit an additional 1100 pregnant women, yielding 990 more children, for a total of 1560 mother-child pairs (88% retention by completion of study) with data and biospecimens to be integrated into the ECHO Consortium. To accomplish this, we will use our established, proven PROTECT/CRECE infrastructure and our experience in recruitment, follow up, sample and data collection, management and analysis, to (a) recruit pregnant women, (b) collect and analyze biological samples during pregnancy, at birth and at annual child visits through age 5, and (c) collect detailed demographic, health, and exposure information collected through questionnaires, evaluations and medical record abstraction during pregnancy, at birth and at annual child visits through age 5. In addition, the multidisciplinary ECHO-PRO team will study (using novel statistical methods for analysis of mixtures) the impact of multiple environmental exposures and exposure mixtures; specifically the relationship between exposure (maternal, in utero and/or during early childhood) to common mixtures of environmental contaminants (air pollution, metals, polycyclic aromatic hydrocarbons, phthalates, phenols, parabens), as well as their mechanistic mediators and modifying factors, on the four ECHO outcome domains: (1) adverse birth outcomes, including preterm birth, reduced fetal growth, and birth defects, (2) obesity, including maternal gestational glycemia and measures of child adiposity and cardiometabolic health, (3) neurodevelopment, including measures of child personal-social, adaptive, motor, communication and cognitive abilities and (4) respiratory health, including measures of child cardiorespiratory patterning, lung volume, and respiratory symptoms. Finally, ECHO-PRO will integrate and compare data obtained through our cohort with the overall ECHO data to better understand the environmental influences on child health outcomes in Puerto Rico and the U.S. mainland.